Is PRICKLE1 p.Phe428= (c.1284T>C) pathogenic?

PRICKLE1 p.Phe428= (c.1284T>C) is classified Likely benign in PRICKLE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). Rare (popmax 0.1%, eas); Associated with epilepsy, progressive myoclonic, 1B.

What condition is associated with PRICKLE1 p.Phe428= (c.1284T>C)?

PRICKLE1 p.Phe428= (c.1284T>C) is associated with epilepsy, progressive myoclonic, 1B (ClinVar).

How common is PRICKLE1 p.Phe428= (c.1284T>C) in the general population?

PRICKLE1 p.Phe428= (c.1284T>C) is rare (popmax 0.1%, eas) (gnomAD).

PRICKLE1 p.Phe428=

c.1284T>C · rs183742526 · VCV537251

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.1%, eas)

Conditions

epilepsy, progressive myoclonic, 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -1.9, phastCons 0.98
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% East Asian · 45/44,866 alleles

Filtering AF 0.077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0688%

Overall 0.00285% 46/1,614,040 alleles · rare exomes 40/1,461,892 · genomes 6/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.1%	997
Remaining individualsnot grpmax-eligible	0.0016%	62,498

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRICKLE1
Protein: p.Phe428=
Coding: c.1284T>C
MANE Select: NM_153026
dbSNP: rs183742526
Type: single nucleotide variant
Location: chr12:42464750 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.55

Full PRICKLE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, progressive myoclonic, 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRICKLE1 c.1639+4C>T Uncertain significance ★★ same condition
PRICKLE1 c.384+6C>A Uncertain significance ★★ same condition
PRICKLE1 p.Ala142Thr Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala145Val Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala34Thr Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala34Val Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala492Thr Uncertain significance ★★ ⚠ same condition
PRICKLE1 p.Ala506Thr Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prickle1-p-phe428 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown